Treatment of refractory Hodgkin’s disease with an anti-CD16/CD30 bispecific antibody |
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Authors: | Cristoph Renner Frank Hartmann M Pfreundschuh |
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Institution: | (1) Medical Department I, Saarland University, D-66424 Homburg, Germany Tel. +49-6841-16-3002; Fax +49-6841-16-3101, DE |
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Abstract: | A group of 15 patients with refractory Hodgkin′s disease were treated in a phase I/II trial with the natural-killer (NK)-cell-activating
bispecific monoclonal antibody HRS-3/A9, which is directed against the Fcγ receptor III (CD16 antigen) and the Hodgkin’s associated
CD30 antigen. The antibody was given four times every 3 – 4 days, starting with 1 mg/m2. The treatment was well tolerated and the maximum tolerated dose was not reached at 64 mg/m2. Side-effects were rare and consisted of fever, pain in involved lymph nodes and a maculopapulous rash. Nine patients developed
human anti-(mouse immunoglobulin) antibodies. One complete and one partial remission (lasting 5 and 3 months, respectively),
three minor responses (1 to 11+ months), and one mixed response were achieved. There was no clear-cut dose side-effect or
dose/response correlation. NK cell activity increased in most of the patients treated with 4 mg/m2 or higher doses but lasted no longer than 6 weeks after therapy. Our results encourage further clinical trials with this novel
immunotherapeutic approach and emphasize the necessity to reduce the immunogenicity of the antibody to allow retreatment of
responding patients.
Accepted: 14 October 1997 |
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Keywords: | Hodgkin’ s lymphoma Bispecific antibodies Natural killer cells |
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